Analysis of cystic fibrosis transmembrane conductance regulator mutations in a cohort of cystic fibrosis patients from Eastern India

Context: Recent studies show that cystic fibrosis (CF) is not rare in Africa and Asia, including the Indian subcontinent, with unique CF transmembrane conductance regulator ( CFTR ) gene variants in these populations. India’s genetic diversity presents challenges for CFTR variant profiling, with distinct mutation patterns across regions. Aims: This study aimed to identify CFTR mutations in children with CF from West Bengal and adjoining states and to analyze genotype–phenotype correlations compared to other Indian regions. Settings and Design: A prospective cross-sectional study was conducted at the Institute of Child Health, Kolkata (August 2021–August 2022), including 21 diagnosed CF patients (confirmed by sweat chloride test) from the target regions. Subjects and Methods: CFTR gene sequencing was performed using next-generation sequencing, and variants were classified following American College of Medical Genetics and Genomics guidelines. Mutation profiles and clinical data were analyzed and compared with the North American CFTR2 database. Results: Twelve CFTR variants were found in 42 alleles, with F508del (38%) as the most common mutation. Other frequent alleles included 3849 + 10 kbC>T (14%) and V456A, 1161delC, R709X, and 1525-1G>A (each 7%). Two novel variants, c.1334del and c.719T>G, were detected. Patients presented late (mean age: 6 years), with 38% mortality before adulthood, reflecting severe pathogenic variants. Clinical manifestations mostly involved respiratory, gastrointestinal (GI), and nutritional issues; though milder variants lacked GI symptoms. Conclusions: The study highlights the extensive genetic heterogeneity of CFTR mutations in eastern India, differing from other regions. This underscores the need for multicentric studies to develop an inclusive national CF genetic panel to improve diagnosis and treatment strategies, including assessing eligibility for modulator therapies.